The ability to grow and maintain cells in vitro was a significant milestone in the biological sciences. However, traditional cell culture techniques lack the ability to analyze single cells, as opposed to bulk cultures. Population-averaged bulk assays are often inaccurate or misleading due to natural cell-to-cell variability. Further, cell signaling and other biochemical parameters constantly change, making dynamic analysis of cells crucial in understanding how a biological system operates. In response to these limitations, microfluidic cell culture systems have been developed that allow for high throughput and multiplexed culture and analysis of individual cells.
Microfluidic cell culture is a promising technology for applications in drug screening, tissue culturing, toxicity screening, and biologic research and can provide improved biological function, higher quality cell-based data, reduced reagent consumption, and lower cost. The most common approach for manufacturing microfluidic devices is soft lithography of polydimethylsiloxane (PDMS), which allows structures of micrometer resolution to be molded from a hard master. PDMS-based culture systems and devices may include a variety of structures, including various kinds of channels, chambers, barriers, and valves. Each of these components may be networked together in various configurations to create a “lab on a chip” device that can be utilized to conduct a variety of biological experiments. Further, microfluidic cell culture systems can be highly multiplexed, allowing for multiple conditions or samples to be tested on a single device.
Key benefits of microfluidic cell culture include improved biological function, higher-quality cell-based data, reduced reagent consumption, and lower cost. Further, high quality molecular and cellular sample preparations are important for various clinical, research, and other applications. In vitro samples closely representing their in vivo characteristics can potentially benefit a wide range of molecular and cellular applications. Handling, characterization, culturing, and visualization of cells or other biologically or chemically active materials (such as beads coated with various biological molecules) have become increasingly valued in the fields of drug discovery, disease diagnoses and analysis, and a variety of other therapeutic and experimental work.
The relatively small scale and multiplexed nature of microfluidic devices results in high applicability to automation. Automated systems are particularly useful in the pharmaceutical industry, which relies on high throughput screening of libraries of chemical compounds to find potential drug candidates. By using microfluidic devices, high throughput screening can test many discrete compounds in parallel so that large numbers of test compounds are screened for biological activity simultaneously. In such systems, pneumatic control is often used to load cells and drive other actions on a microfluidic device. However, imperfect sealing of a pneumatic control system to a microfluidic device may result in improper pressures being applied to the device, thus biasing the results of the analysis. Connections between the pneumatic control system and microfluidic device, such as gas line tubing, may also become contaminated, requiring either disposal, or extensive and manual cleaning.